The purpose of this project is to determine the incidence rates, rates of progression, and risk factors for the chronic complications of type 2 diabetes. The study is conducted in the Pima Indians of the Gila River Indian Community, who have participated in a longitudinal epidemiologic study since 1965 (see project Z01 DK 69000). Risk factors for the major complications of diabetes, retinopathy, nephropathy, and coronary artery disease, are determined by longitudinal follow-up of diabetic subjects. Methods of ascertainment of these complications include fundus photography, measurement of urine albumin and serum creatinine concentrations, and electrocardiography. The incidence of diabetic nephropathy, as a function of duration of diabetes, was similar in those with diabetes onset in youth compared with older onset diabetes, and the rate of retinopathy was only slightly lower in youth. Thus, by the time they reach middle adult years, Pima Indians with youth-onset diabetes have rates of advanced diabetes complications similar to those of older adults who have had diabetes for the same length of time. Periodontal disease, a common infectious complication of diabetes, more than doubled the incidence rate of fatal heart disease in Pima Indian adults with diabetes. We continue to search for genetic determinants of diabetic complications, including a genome-wide linkage study of diabetic retinopathy and a multicentered genetic linkage study (Family Investigation of Nephropathy and Diabetes) of diabetic nephropathy in an attempt to identify susceptibility genes for nephropathy. Several positional candidate genes are being evaluated.